Summary of cGVHD pivotal trials
Drug/pivotal study design . | Ibrutinib phase 1b/2, open-label study5 . | Ruxolitinib phase 3 open-label, randomized trial (REACH3)6 . | Belumosudil phase 2 randomized, multicenter registration (ROCKstar Study)7 . | Axatilimab phase 2, multinational, pivotal, randomized study (AGAVE-201)8 . | Rovadicitinib multicenter, open-label, phase 1b/2a . |
---|---|---|---|---|---|
Target and mechanism of action | BTK inhibitor | JAK1/2 inhibitor | ROCK2 inhibitor | CSF1R blocking antibody | Dual JAK1/2 and ROCK1/2 inhibitor |
Reduced activation, proliferation, and survival of B and T cells | Reduced inflammation, increased TREGs, reduced collagen deposition | Reduced type 17 and follicular T-helper cells and enhanced regulatory T cells | Inhibition of monocyte-driven inflammation and fibrosis | Combined inhibition of inflammatory and profibrotic pathways | |
Study population | N = 42 | N = 329 | N = 132 | N = 241 | N = 44 |
Age 18 years | Age > 12 years | Age > 12 years | Age > 2 years | Age > 12 years | |
1-3 lines of therapy cGVHD | 1 prior line | 2-5 prior lines of therapy | ≥2 lines of therapy | ≥1 prior lines of therapy | |
Steroid-refractory: 14% Steroid-dependent: 67% | Steroid-refractory: 71.4% Steroid-dependent: 28.6% | Refractory to prior line treatment: 72% | Refractory to last line of treatment: 48% | Steroid-refractory: 25% Steroid-dependent: 75% | |
Lung involvement: 5% | Lung involvement: 44.8% Lung score 3: 8.5%: | Lung involvement: 36% Lung score 3: excluded | Lung involvement: 40% | Lung involvement: 59.1% Lung score 3: 23.1% | |
Prior rux: 29% Prior ibru: 34% | Prior rux: 74% Prior belu: 23% | Prior rux: 40.9% Prior belu: 0 | |||
Short-term efficacy | BOR (at any time): 67% | BOR until week 24: 76.4% | BOR∗ (at any time): 76% | ORR in first 6 cycles∗: 74% | BOR until week 24: 86.4% |
Long-term efficacy | Sustained response beyond 44 weeks: 55% | Median FFS above 18.6 mo | 12-mo FFS∗: 57% | 12-mo FFS∗: 64% | 12-mo FFS: 85.2% |
AEs leading to discontinuation | 33% | 16.4% | 21% | 6%∗ | 3.5%∗ |
Drug/pivotal study design . | Ibrutinib phase 1b/2, open-label study5 . | Ruxolitinib phase 3 open-label, randomized trial (REACH3)6 . | Belumosudil phase 2 randomized, multicenter registration (ROCKstar Study)7 . | Axatilimab phase 2, multinational, pivotal, randomized study (AGAVE-201)8 . | Rovadicitinib multicenter, open-label, phase 1b/2a . |
---|---|---|---|---|---|
Target and mechanism of action | BTK inhibitor | JAK1/2 inhibitor | ROCK2 inhibitor | CSF1R blocking antibody | Dual JAK1/2 and ROCK1/2 inhibitor |
Reduced activation, proliferation, and survival of B and T cells | Reduced inflammation, increased TREGs, reduced collagen deposition | Reduced type 17 and follicular T-helper cells and enhanced regulatory T cells | Inhibition of monocyte-driven inflammation and fibrosis | Combined inhibition of inflammatory and profibrotic pathways | |
Study population | N = 42 | N = 329 | N = 132 | N = 241 | N = 44 |
Age 18 years | Age > 12 years | Age > 12 years | Age > 2 years | Age > 12 years | |
1-3 lines of therapy cGVHD | 1 prior line | 2-5 prior lines of therapy | ≥2 lines of therapy | ≥1 prior lines of therapy | |
Steroid-refractory: 14% Steroid-dependent: 67% | Steroid-refractory: 71.4% Steroid-dependent: 28.6% | Refractory to prior line treatment: 72% | Refractory to last line of treatment: 48% | Steroid-refractory: 25% Steroid-dependent: 75% | |
Lung involvement: 5% | Lung involvement: 44.8% Lung score 3: 8.5%: | Lung involvement: 36% Lung score 3: excluded | Lung involvement: 40% | Lung involvement: 59.1% Lung score 3: 23.1% | |
Prior rux: 29% Prior ibru: 34% | Prior rux: 74% Prior belu: 23% | Prior rux: 40.9% Prior belu: 0 | |||
Short-term efficacy | BOR (at any time): 67% | BOR until week 24: 76.4% | BOR∗ (at any time): 76% | ORR in first 6 cycles∗: 74% | BOR until week 24: 86.4% |
Long-term efficacy | Sustained response beyond 44 weeks: 55% | Median FFS above 18.6 mo | 12-mo FFS∗: 57% | 12-mo FFS∗: 64% | 12-mo FFS: 85.2% |
AEs leading to discontinuation | 33% | 16.4% | 21% | 6%∗ | 3.5%∗ |
belu, belumosudil; CSF1R, colony-stimulating factor 1 receptor; FFS, failure-free survival; Ibru, ibrutinib); JAK, Janus kinase; ORR, overall response; ROCK, rho-associated coiled-coil-containing protein kinase; rux, ruxolitinib; TREGs, regulatory T cells.
Data for patients treated with recommended or approved dose.